Clinical and laboratory data for patients treated with emapalumab and eculizumab for graft rejection
| . | Patient 19 . | Patient 22 . |
|---|---|---|
| Age, y | 12 | 10 |
| Sex | Male | Female |
| Diagnosis | Severe aplastic anemia | Genetically undefined chromosomal fragility syndrome |
| HCT 2 | ||
| Conditioning | Fludarabine | Alemtuzumab/fludarabine/melphalan |
| Graft | PBSC | PBSC |
| Donor | 8/10, URD | 8/10, URD |
| GVHD PPx | Ex vivo T-cell depletion | Ex vivo T-cell depletion |
| Cell dose (CD34+ cells × 106/kg) | 13.6 | 37.6 |
| Days from first HCT | 38 | 72 |
| Fevers | ||
| Tmax (°F) | 104.7 | 104.9, 103.1* |
| Tmax day | Day +15 | Day +9, day +21 Patient 22 was afebrile for 3 d in between fever episodes. Early fevers were diagnosed as engraftment syndrome and the later fevers attributed to rejection. |
| Interferon γ (CXCL9, pg/mL) | ||
| Day emapalumab given | Day +16 | Day +21 |
| CXCL9 baseline | <31 | 36 |
| CXCL9 pre-emapalumab | 149 (day +15) | 271 (day +21) |
| CXCL9 post-emapalumab | 49 (day +18) | 226 (day +22), 76 (day +24) |
| Subsequent CXCL9 studies | All additional CXCL9 levels were normal with a maximum of value 40. The last recorded levels was <31 on day +91. | CXCL9 was remeasured on day +35 and was <31. No additional CXCL9 levels were measured for graft rejection surveillance. |
| Terminal complement (sC5b9, ng/mL) | ||
| Day eculizumab given | Day +16 | Day +21 |
| sC5b-9 baseline | 57 | 59 |
| sC5b-9 pre-eculizumab | 92 (day +15) | 234 (day +21) |
| sC5b-9 post eculizumab | 156 (day +17) | 223 (day +35), 152 (day +38) |
| Subsequent sC5b-9 studies | Repeat levels on day +20, day +24, and day +26 were 122, 150, and 139, respectively. No additional increases were observed, and the last recorded level was 104 on day +98. | sC5b-9 levels were measured for graft rejection surveillance through day +48 and the last recorded value was 187. |
| Donor chimerism | ||
| Before eculizumab/emapalumab | 98% (day +14) | 93% (day +19) |
| After eculizumab/emapalumab | 97% (day +17) | 96% (day +23), 97% (day +25) |
| Long term | Donor chimerism dropped to 91% on day +24 but recovered and largely remained ≥95%. The most recent donor chimerism was 95% on day +371. | Donor chimerism remained ≥98% and the majority of measurements were 100% including on day +95, shortly before death. |
| . | Patient 19 . | Patient 22 . |
|---|---|---|
| Age, y | 12 | 10 |
| Sex | Male | Female |
| Diagnosis | Severe aplastic anemia | Genetically undefined chromosomal fragility syndrome |
| HCT 2 | ||
| Conditioning | Fludarabine | Alemtuzumab/fludarabine/melphalan |
| Graft | PBSC | PBSC |
| Donor | 8/10, URD | 8/10, URD |
| GVHD PPx | Ex vivo T-cell depletion | Ex vivo T-cell depletion |
| Cell dose (CD34+ cells × 106/kg) | 13.6 | 37.6 |
| Days from first HCT | 38 | 72 |
| Fevers | ||
| Tmax (°F) | 104.7 | 104.9, 103.1* |
| Tmax day | Day +15 | Day +9, day +21 Patient 22 was afebrile for 3 d in between fever episodes. Early fevers were diagnosed as engraftment syndrome and the later fevers attributed to rejection. |
| Interferon γ (CXCL9, pg/mL) | ||
| Day emapalumab given | Day +16 | Day +21 |
| CXCL9 baseline | <31 | 36 |
| CXCL9 pre-emapalumab | 149 (day +15) | 271 (day +21) |
| CXCL9 post-emapalumab | 49 (day +18) | 226 (day +22), 76 (day +24) |
| Subsequent CXCL9 studies | All additional CXCL9 levels were normal with a maximum of value 40. The last recorded levels was <31 on day +91. | CXCL9 was remeasured on day +35 and was <31. No additional CXCL9 levels were measured for graft rejection surveillance. |
| Terminal complement (sC5b9, ng/mL) | ||
| Day eculizumab given | Day +16 | Day +21 |
| sC5b-9 baseline | 57 | 59 |
| sC5b-9 pre-eculizumab | 92 (day +15) | 234 (day +21) |
| sC5b-9 post eculizumab | 156 (day +17) | 223 (day +35), 152 (day +38) |
| Subsequent sC5b-9 studies | Repeat levels on day +20, day +24, and day +26 were 122, 150, and 139, respectively. No additional increases were observed, and the last recorded level was 104 on day +98. | sC5b-9 levels were measured for graft rejection surveillance through day +48 and the last recorded value was 187. |
| Donor chimerism | ||
| Before eculizumab/emapalumab | 98% (day +14) | 93% (day +19) |
| After eculizumab/emapalumab | 97% (day +17) | 96% (day +23), 97% (day +25) |
| Long term | Donor chimerism dropped to 91% on day +24 but recovered and largely remained ≥95%. The most recent donor chimerism was 95% on day +371. | Donor chimerism remained ≥98% and the majority of measurements were 100% including on day +95, shortly before death. |
GVHD, graft-versus-host disease; PPx, prophylaxis; URD, unrelated donor after second HCT.